Mesenchymal stem cells stimulate protective genetic reprogramming of injured cardiac ventricular myocytes

► A mixed coculture of human mesenchymal stem cells and mouse cardiac myocytes exposed to agents that recapitulate stress and injury to determine if stems cells have direct beneficial effects on cardiac cells. ► Inflammatory-like cardiac damage, evoked by lipopolysaccaharide (LPS )and IL-1β in this cell setting is mediated by signaling evoked by the proinflammatory cytokine, IL-18. ► hMSCs are powerful benefactors of cardiac myocytes as normal Ca2+ signaling is maintained in the presence of these damaging stimuli. ► hMSC-derived factors act in a reparative fashion, restoring normal function to damaged cardiac myocytes. ► hMSCs provoke a genetic reprogramming of cardiac myocytes manifest by alterations in the pattern of cytokine release and attenuation of the activation of proinflammatory transcription factor, NFκB.